BACKGROUND Circulating C3 levels are elevated in obese patients, but how this factor is affected after weight loss through diet is a question that is yet unanswered. Therefore, the aim of this study was to evaluate the effects of weight loss on lipid and hydrocarbonated metabolism parameters and on the levels of C3 and C4 components of complement in obese patients. METHODS This is a longitudinal intervention study based on a 6-week very low-calorie diet (VLCD), a liquid formula of 603 kcal/day. A total of 131 middle-aged patients were distributed among grades II, III and IV of obesity. Anthropometric parameters, total cholesterol, triglycerides, high-density lipoprotein cholesterol, LDLc, apolipoproteins A-I and B-100, glucose, insulin, HOMA-IR and C3 and C4 levels were evaluated at baseline and after 6 weeks of intervention. RESULTS After VLCD, the moderate weight loss was accompanied by a significant reduction in C3 levels in grade III and grade IV patients (10.2% and 15.4%, respectively; P < 0.001). C4 levels were not altered. Adherence to the diet improved anthropometric parameters and was accompanied by a significant decrease in all lipid profile parameters (P < 0.001). In addition, weight loss was associated with an improvement in hydrocarbonated metabolism as shown by the decrease in glucose levels and HOMA-IR (P < 0.01). CONCLUSIONS Our findings show that in severely obese patients following a VLCD for 6 weeks produces reductions in factor C3, a biomarker of cardiovascular disease, and a significant improvement in some features of metabolic syndrome. In this way, the abovementioned diet may represent an effective strategy for treating obesity and related cardiovascular risk factors.